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방광 평활근 운동에 대한 펩타이드 전달 인자의 영향

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[영문] [한글] 방광의 부교감 신경을 전기 자극하면 방광근의 수축이 일어나나 이러한 작용이 atropin e전처치로 완전히 억압되지 않음은 이미 잘 알려진 사실이며, 또한 방광에 분포하는 절후 신경섬유의 일부는 '비 코린성'일 것이라고 주장되고 있다. 한편 Hokfelt등(1978)은 방 광에서 면역조직화학적 방법으로 substance P가 존재함을 보고하였고, Erspamer등(1973) 은 substance P 및 bombesin이 방광근의 수축을 항진시키며 이러한 작용은 atropine으로 봉쇄되지 않고, acetylcholine보다 효력이 강하다고 하여, substance P등 peptide들이 ' 비 코린성 비 아드레나린성'효과의 전달 물질로 작용할 수 있을 것이라는 가능성을 제시 하였다. 본 실험에서는 흰쥐 방광 절편에 대한 substance P, bombesin, cholecystokinin octape ptide(CCK-OP), pentagastrin등 peptide성 인자의 작용을 검색하였으며 그 결과는 다음과 같다. 1. Substance P, bombesin, acetylcholine은 흰쥐 방광 절편의 수축운동을 항진시키며, 작용지속 시간은 substance P의 경우 수분간 지속되고 bombesin의 경우는 30분 이상 유 지되나, acetylcholine의 작용은 1분 이내에 소실되었다. pD^^2 치는 substance P가 8.05±0.05, bombesin이 8.29±0.09로 acetylcholine의 pD^^ 2 치인 5.32±0.07 보다 월등히 컸으나, 최고 효능은 acetylcholine보다 다소 낮았다. 2. CCK-OP와 pentagastrin은 흰쥐 방광 절편 운동에 아무런 영향이 없었다. 3. 흰쥐 방광 절편에서 substance P 및 bombesin의 수축운동 항진효과는 atropine, phe ntolamine, propranolol, chlorpheniramine, proglumide 또는 quinidine전처치로 봉쇄되 지 않았다. 4. Tyrode액내 calcium을 제거함으로 acetylcholine, substance P, bombesin의 방광근 수축작용이 소실되었으나, 다시 calcium을 보충함으로 급격한 긴장도의 증가와 규칙직인 수축 운동이 나타났다. 5. Diltiazem 전처치로 substance P 및 bombesin의 방광근 수축 작용은 소실되었다. 이상의 결과로 보아 substance P 및 bombesin은 흰쥐 방광 절편의 '비 아드레나린성 비 코린성' 수축 운동에 관여하며 이의 작용은 calcium의 세포내 이동과 관련된다고 생각한 다 Peptidergic Influences on the Motility of Rat Urinary Bladder Dong Chul Shin Department of Medical Science The Graduate School, Yonsei, University (Directed by Professor Sa Suk Hong, M.D.) It has long been known that the contraction of urinary bladder elicited by parasympathetic stimulation is not completely blocked by atropine. This phenomenon is believed to he mediated in part by 'non-cholinergic' mechanism, and is also suggested that most of the postganglionic fibers in the urinary bladder possibly contains the 'non-cholinergic' components. Meanwhile, Erspamer et al(1973) reported that substance P and bombesin could enhance the atropine-resistant contraction of detrusor muscle in the rat, which were stronger than that produced with acetylcholine. Moreover, Hokfelt(1978) demonstrated the presence of substance P in bladder by means of immunohistochemical methods. Such evidences suggest the possibility that these peptides may indeed serve as a factors for the atropine-resistant contraction of detrusor muscle. In the present study, the effects of substance P, bombesin and several other peptides were examined in view of the possible mediators for the contraction of rat bladder under various in vitro pharmacological conditions. The following results ware obtained. 1. Substance P, bombesin, and acetylcholine elicited the contraction of rat detrusor muscle. The evoked contractions persisted for 30 minutes or longer in the presence of bombesin and the action of substance P lasted for a few minutes, however, the acetylcholine evoked contraction was transient. The pD^^2 values of substance P and bombesin were 8.05±0.05 and 8.29±0.09, respectively, and these values were much higher than that obtained with acetylcholine, which was 5.32±0.07. 2. Cholecystokinin octapeptide(CCK-OP) and pentagastrin had little effects on the motility of rat detrusor muscle. 3. Several known blookers such as atropine(non-selective antimuscarinics), phentolamine(adrenergic α-receptor antagonist), propranolol(adrenergic β-recptor antagonist), chlorpheniramine(histamine H^^1-blocker), proglumide(gastrin/CCK blocker) and quinidine(purinergic blocker) could not block the contraction of rat detrusor induced by substance P or by bombesin. 4. In calcium-free Tyrode buffer, substance P and bombesin did not elicit any contraction of the detrusor. However, addition of calcium into the buffer, rapid increase of tonus was occured and then regular contraction was followed. 5. Diltiazem, a calcium entry blocker, abolished the enhancement of contractility induced by substance P or bombesin. By these results, it is concluded that peptides such as substance P and bombesin enhanced the motility of rat urinary bladder in a 'non-cholinergic non-adrenergic' manner, and further the presence of calcium and increased influx of external calcium appears inevitable for such responses as well as contractions.
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